Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

Quick Takes

  • Elevated Lp(a) is associated with accelerated progression of low-attenuation plaque independent of traditional risk factors.
  • The study strongly supports measuring Lp(a) to identify persons with a high lifetime risk for atherosclerotic cardiovascular disease (ASCVD) and plays an important role for antisense therapies targeting Lp(a).
  • Low-attenuation plaque on CCTA is a quantitative marker of necrotic core and provides prognostic information for cardiovascular outcomes. In the SCOT-HEART trial, the burden of low-attenuation plaque was the most powerful predictor of fatal or nonfatal myocardial infarction, outperforming cardiovascular risk scores, assessments of plaque lumen stenosis, CT calcium scoring, and the burden of all other different plaque subtypes.
  • There will be increasing value for CCTA in the detection and treatment of ASCVD.

Study Questions:

Is lipoprotein(a) [Lp(a)] associated with adverse plaque progression?


Participants were recruited as part of the DIAMOND (Dual Antiplatelet Therapy to Inhibit Coronary Atherosclerosis and Myocardial Injury in Patients With Necrotic High-Risk Coronary Plaque Disease) study, a double-blind, randomized, parallel group, placebo-controlled trial conducted at a single center in Edinburgh, United Kingdom. Lp(a) was measured in patients with advanced stable coronary artery disease (CAD) (≥2 major epicardial vessels with any combination of either >50% luminal stenosis or previous percutaneous coronary intervention or coronary artery bypass grafting). Coronary computed tomography angiography (CCTA) was obtained at baseline and 12 months to assess progression of total, calcific, noncalcific, and low attenuation plaque (necrotic core) in particular. High Lp(a) was defined as ≥70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein cholesterol, diabetes, rheumatoid arthritis, and deprivation index).


A total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, of whom 43 (22.5%) had a high Lp(a). Seventy-two percent had prior acute coronary syndrome, 95% were on statins, and all were on antiplatelet therapy. The median serum Lp(a) concentration was 15 mg/dL (interquartile range, 6-58 mg/dL) and the 80th percentile was 78 mg/dL; median Lp(a) value of 100 (range, 82-115) mg/dL and 10 (range, 5-24) mg/dL in the high and low Lp(a) groups, respectively. Repeat CCTA after 12 months was available in 83.8%. At baseline, there was no difference in CAD severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm3 vs. -0.7 ± 50.1 mm3; p = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp[a], 95% confidence interval, 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression.


Among patients with advanced stable CAD, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.


The study was not designed specifically to assess Lp(a). The published results of the DIAMOND study showed that dual antiplatelet therapy did not impact coronary atherosclerotic disease progression or adverse plaque phenotype by CCTA, which made it very cost-effective for the analysis.

Keywords: Acute Coronary Syndrome, Atherosclerosis, Computed Tomography Angiography, Constriction, Pathologic, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Diagnostic Imaging, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoprotein(a), Myocardial Infarction, Percutaneous Coronary Intervention, Plaque, Atherosclerotic, Platelet Aggregation Inhibitors, Primary Prevention, Risk Factors

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